Loneliness and cardiovascular reactivity to acute stress in older adults.

Loneliness has been linked to cardiovascular health outcomes in older adulthood. One proposed mechanism by which loneliness influences cardiovascular health is through atypical cardiovascular reactivity (CVR) to stress. This study is an examination of loneliness and CVR in older adults, comparing associations across two stressors and two commonly used measures of loneliness, with a particular focus on underlying hemodynamic variables including cardiac output, total peripheral resistance, and ejection time (EJT). Eighty older adults, ranging in age from 55 to 88 years (M = 68.93, SD = 8.28), completed two versions of the UCLA loneliness scale (a 20-item and a briefer, three-item) and took part in a laboratory stress-testing procedure which included a mental arithmetic challenge and a public speaking task. Cardiovascular activity was monitored continuously throughout. For the 20-item version of the UCLA loneliness scale, loneliness was not significantly related to CVR, and was only significantly associated with lower levels of overall EJT. For the three-item version of the UCLA, no associations withstood adjustment for multiple testing. Loneliness was not reliably associated with CVR. Further, although greater loneliness was related to lower levels of overall EJT, this was only observed for the 20-item scale. The findings do not strongly provide support for reactivity to acute stress as a pathway linking loneliness to disease outcomes, and highlight key methodological issues related to the assessment of loneliness-reactivity associations for future.

Type D personality and cardiovascular reactivity to acute stress: The mediating effects of social support and negative social relationships.

Type D personality has been consistently associated with adverse cardiovascular health with atypical cardiovascular reactions to psychological stress one potential underlying mechanism. As Type D individuals have been noted to report lower social support and greater perceptions of negativity in social interactions, this study examined if the association between Type D personality and cardiovascular reactivity was mediated by these social relationships. A sample of 195 undergraduate students (138 female) participated in this observational study, where they completed measures assessing Type D personality (DS14), social support, and perceptions of negative social relationships (National Institute of Health social relationship scales), before undergoing a traditional cardiovascular reactivity protocol. Systolic and diastolic blood pressure (SBP; DBP), heart rate (HR), cardiac output (CO), and total peripheral resistance (TPR) were monitored throughout. ANCOVAs and regressions indicated that Type D personality was associated with lower cardiovascular reactivity to a mental arithmetic stressor. Furthermore, mediation analyses (process macro) indicated that the relationship between Type D personality and cardiovascular reactivity was mediated via increased perceptions of negative social relationships, as well as lower levels of social support. Apart from a significant association between Type D personality and increased HR reactivity, all results failed to withstand adjustment for the individual effects of negative affect (NA) and social inhibition (SI) in controlled analyses. Overall, these findings suggest that the predictive utility of Type D personality on cardiovascular reactivity above and beyond the individual effects of NA and SI is limited, and may vary depending on the cardiovascular parameter of focus.

Exosome reporter mice reveal the involvement of exosomes in mediating neuron to astroglia communication in the CNS.

Astroglia play active and diverse roles in modulating neuronal/synaptic functions in the CNS. How these astroglial functions are regulated, especially by neuronal signals, remains largely unknown. Exosomes, a major type of extracellular vesicles (EVs) that originate from endosomal intraluminal vesicles (ILVs), have emerged as a new intercellular communication process. By generating cell-type-specific ILVs/exosome reporter (CD63-GFPf/f) mice and immuno-EM/confocal image analysis, we found that neuronal CD63-GFP+ ILVs are primarily localized in soma and dendrites, but not in axonal terminals in vitro and in vivo. Secreted neuronal exosomes contain a subset of microRNAs (miRs) that is distinct from the miR profile of neurons. These miRs, especially the neuron-specific miR-124-3p, are potentially internalized into astrocytes. MiR-124-3p further up-regulates the predominant glutamate transporter GLT1 by suppressing GLT1-inhibiting miRs. Our findings suggest a previously undescribed neuronal exosomal miR-mediated genetic regulation of astrocyte functions, potentially opening a new frontier in understanding CNS intercellular communication.

Loneliness and cardiovascular reactivity to acute stress in younger adults.

Loneliness is connected to poorer health outcomes with stress reactivity proposed as an underlying mechanism. The present study explored whether the relationship between loneliness and cardiovascular reactivity (CVR) varies across acute psychological stress tasks. Eighty-eight healthy younger adults completed a psychometric measure of loneliness and participated in a standardised cardiovascular stress-testing protocol, with a public speaking and a mental arithmetic task. Cardiovascular functioning was assessed before and during the acute stress exposure. Higher levels of loneliness significantly predicted lower total peripheral resistance (TPR) reactivity to the public speaking task but not to the arithmetic challenge. This suggests that the effect of loneliness on cardiovascular reactivity to acute stress may vary by stressor type. These findings are discussed in relation to future research.

Loneliness and acute stress reactivity: A systematic review of psychophysiological studies.

Physiological reactivity to acute stress has been proposed as a potential biological mechanism by which loneliness may lead to negative health outcomes such as cardiovascular disease. This review was conducted to investigate the association between loneliness and physiological responses to acute stress. A series of electronic databases were systematically searched (PsycARTICLES, PsycINFO, Medline, CINAHL Plus, EBSCOhost, PubMed, SCOPUS, Web of Science, Science Direct) for relevant studies, published up to October 2016. Eleven studies were included in the review. Overall, the majority of studies reported positive associations between loneliness and acute stress responses, such that higher levels of loneliness were predictive of exaggerated physiological reactions. However, in a few studies, loneliness was also linked with decreased stress responses for particular physiological outcomes, indicating the possible existence of blunted relationships. There was no clear pattern suggesting any sex- or stressor-based differences in these associations. The available evidence supports a link between loneliness and atypical physiological reactivity to acute stress. A key finding of this review was that greater levels of loneliness are associated with exaggerated blood pressure and inflammatory reactivity to acute stress. However, there was some indication that loneliness may also be related to blunted cardiac, cortisol, and immune responses. Overall, this suggests that stress reactivity could be one of the biological mechanisms through which loneliness impacts upon health.

MicroRNA-containing extracellular vesicles released from endothelial colony-forming cells modulate angiogenesis during ischaemic retinopathy.

Endothelial colony-forming cells (ECFCs) are a defined subtype of endothelial progenitors that modulate vascular repair and promote perfusion in ischaemic tissues. Their paracrine activity on resident vasculature is ill-defined, but mediated, at least in part, by the transfer of extracellular vesicles (EVs). To evaluate the potential of isolated EVs to provide an alternative to cell-based therapies, we first performed a physical and molecular characterization of those released by ECFCs. Their effects upon endothelial cells in vitro and angiogenesis in vivo in a model of proliferative retinopathy were assessed. The EVs expressed typical markers CD9 and CD63 and formed a heterogeneous population ranging in size from ~60 to 1500 nm by electron microscopy. ECFC EVs were taken up by endothelial cells and increased cell migration. This was reflected by microarray analyses which showed significant changes in expression of genes associated with angiogenesis. Sequencing of small RNAs in ECFCs and their EVs showed that multiple microRNAs are highly expressed and concentrated in EVs. The functional categories significantly enriched for the predicted target genes of these microRNAs included angiogenesis. Intravitreally delivered ECFC EVs were associated with the vasculature and significantly reduced the avascular area in a mouse oxygen-induced retinopathy model. Our findings confirm the potential of isolated EVs to influence endothelial cell function and act as a therapy to modulate angiogenesis. The functions associated with the specific microRNAs detected in ECFC EVs support a role for microRNA transfer in mediating the observed effects.

Performance feedback, self-esteem, and cardiovascular adaptation to recurring stressors.

BACKGROUND AND OBJECTIVES: This study sought to examine the effects of performance feedback and individual differences in self-esteem on cardiovascular habituation to repeat stress exposure. METHODS: Sixty-six university students (n = 39 female) completed a self-esteem measure and completed a cardiovascular stress-testing protocol involving repeated exposure to a mental arithmetic task. Cardiovascular functioning was sampled across four phases: resting baseline, initial stress exposure, a recovery period, and repeated stress exposure. Participants were randomly assigned to receive fictional positive feedback, negative feedback, or no feedback following the recovery period. RESULTS: Negative feedback was associated with a sensitized blood pressure response to a second exposure of the stress task. Positive feedback was associated with decreased cardiovascular and psychological responses to a second exposure. Self-esteem was also found to predict reactivity and this interacted with the type of feedback received. CONCLUSIONS: These findings suggest that negative performance feedback sensitizes cardiovascular reactivity to stress, whereas positive performance feedback increases both cardiovascular and psychological habituation to repeat exposure to stressors. Furthermore, an individual's self-esteem also appears to influence this process.

Rapid quantification of microRNAs in plasma using a fast real-time PCR system.

The ability to rapidly detect circulating small RNAs, in particular microRNAs (miRNAs), would further increase their already established potential as biomarkers for a range of conditions. One rate-limiting factor in miRNA detection is the time taken to perform quantitative real-time PCR (qPCR) amplification. We therefore evaluated the ability of a novel thermal cycler to perform this step in less than 10 minutes. Quantitative PCR was performed on an xxpress thermal cycler (BJS Biotechnologies), which employs a resistive heating system and forced air cooling to achieve thermal ramp rates of 10°C/s, and a conventional Peltier-controlled LightCycler 480 system (Roche) ramping at 4.8°C/s. The quantification cycle (Cq) for detection of 18S rDNA from a standard genomic DNA sample was significantly more variable across the block (F-test, P = 2.4 × 10(-25)) for the xxpress (20.01 ± 0.47 sd) than for the LightCycler (19.87 ± 0.04 sd). RNA was extracted from human plasma, reverse transcribed, and a panel of miRNAs was amplified and detected using SYBR Green. The sensitivities of the two systems were broadly comparable-both detected a panel of miRNAs reliably, and both indicated similar relative abundances. The xxpress thermal cycler facilitates rapid qPCR detection of small RNAs and brings point-of-care diagnostics based upon detection of circulating miRNAs a step closer to reality.

Small RNAs from plants, bacteria and fungi within the order Hypocreales are ubiquitous in human plasma.

BACKGROUND: The human microbiome plays a significant role in maintaining normal physiology. Changes in its composition have been associated with bowel disease, metabolic disorders and atherosclerosis. Sequences of microbial origin have been observed within small RNA sequencing data obtained from blood samples. The aim of this study was to characterise the microbiome from which these sequences are derived. RESULTS: Abundant non-human small RNA sequences were identified in plasma and plasma exosomal samples. Assembly of these short sequences into longer contigs was the pivotal novel step in ascertaining their origin by BLAST searches. Most reads mapped to rRNA sequences. The taxonomic profiles of the microbes detected were very consistent between individuals but distinct from microbiomes reported at other sites. The majority of bacterial reads were from the phylum Proteobacteria, whilst for 5 of 6 individuals over 90% of the more abundant fungal reads were from the phylum Ascomycota; of these over 90% were from the order Hypocreales. Many contigs were from plants, presumably of dietary origin. In addition, extremely abundant small RNAs derived from human Y RNAs were detected. CONCLUSIONS: A characteristic profile of a subset of the human microbiome can be obtained by sequencing small RNAs present in the blood. The source and functions of these molecules remain to be determined, but the specific profiles are likely to reflect health status. The potential to provide biomarkers of diet and for the diagnosis and prognosis of human disease is immense.

Pharmacological profiling of store-operated Ca2+ entry in retinal arteriolar smooth muscle.

OBJECTIVE: Pharmacological profiling of SOCE and molecular profiling of ORAI and TRPC expression in arterioles. METHODS: Fura-2-based microfluorimetry was used to assess CPA-induced SOCE in rat retinal arteriolar myocytes. Arteriolar ORAI and TRP transcript expression was screened using RT-PCR. RESULTS: The SKF96365 and LOE908 blocked SOCE (IC(50) s of 1.2 and 1.4 µm, respectively). Gd(3+) and La(3+) potently inhibited SOCE (IC(50) s of 21 and 42 nm, respectively), but Ni(2+) showed lower potency (IC(50) = 11.6 µm). 2APB inhibited SOCE (IC(50) = 3.7 µm) but enhanced basal influx (>100 µm). Verapamil and nifedipine had no effect at concentrations that inhibit L-type Ca(2+) channels, but diltiazem inhibited SOCE by approximately 40% (≥0.1 µm). The RT-PCR demonstrated transcript expression for ORAI 1, 2, and 3, and TRPC1, 3, 4, and 7. Transcripts for TRPV1 and 2, which are activated by 2APB, were also expressed. CONCLUSIONS: The pharmacological profile of SOCE in retinal arteriolar smooth muscle appears unique when compared with other vascular tissues. This suggests that the molecular mechanisms underlying SOCE can differ, even in closely related tissues. Taken together, the pharmacological and molecular data are most consistent with involvement of TRPC1 in SOCE, although involvement of ORAI or other TRPC channels cannot be excluded.